[unreadable] Loss of control from moderate to excessive amounts of drug consumed is one of the hallmarks of human addiction. Previous work has shown that rats self-administering cocaine, when allowed increased access time, will escalate their hourly average intake of the drug. Furthermore, our lab has shown that this escalation phenomenon can be mimicked pharmacologically by the systemic administration of nicotine. The reported co-abuse of cocaine and nicotine has led to an increase in research regarding possible synergistic effects of these two drugs. For example, it has been recently demonstrated that when cocaine addicts are given a dose of nicotine they report an increased sense of craving for cocaine. However, when addicts are given a nicotinic antagonist they report decreased craving. The proposed experiments will determine the ability of cholinergic antagonists to modulate cocaine self-administration behavior in rats. Furthermore, this proposal will determine if the ventral tegmental area is a site-specific participant in the observed phenomena of escalating cocaine intake. Finally, within the ventral tegmental area, we will look at the hypothesized change in extracellular acetylcholine as a function of increased cocaine self-administration. [unreadable] [unreadable] [unreadable] [unreadable]